Vitamin D3 and deconvoluting a rash.
Vitamin D3 and deconvoluting a rash.
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DOI：
10.1172/jci.insight.163789
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发表时间：
2023-01-24
期刊：
影响因子：
8
通讯作者：
Lu, Kurt Q.
中科院分区：
文献类型：
--
作者：
Ernst, Madison K.;Evans, Spencer T.;Techner, Jose-Marc;Rothbaum, Robert M.;Christensen, Luisa F.;Onay, Ummiye Venus;Biyashev, Dauren;Demczuk, Michael M.;Nguyen, Cuong V.;Honda, Kord S.;McCormick, Thomas S.;Tsoi, Lam C.;Gudjonsson, Johann E.;Cooper, Kevin D.;Lu, Kurt Q.
药物不良反应是不可预测的免疫事件，经常给临床管理带来挑战。全身给药胆骨化醇（维生素D3）具有免疫调节特性。在这项随机、双盲、安慰剂对照的健康成人干预试验中，我们研究了单次高剂量口服维生素D3对实验性诱导的化学皮疹的临床和分子免疫调节作用。局部氮芥（NM）诱导28例受试者皮肤炎症。在接下来的一周内，通过临床测量、血清研究和皮肤组织分析来表征参与者对NM的特异性炎症反应。所有参与者在对侧重复NM暴露，然后接受安慰剂或200,000 IU胆钙化醇干预。完成皮疹反应后进行6周多组学分析、临床测量和血清研究。胆骨化醇减轻了所有参与者的急性炎症，并达到了6周的持久反应。皮肤和血液的综合分析发现了对NM反应严重程度的意外差异，系统性中性粒细胞增多和显著的组织病理学和临床差异证实了这一点。多组学和通路分析揭示了3个生物标志物（CCL20, CCL2, CXCL8）对被胆钙化醇抑制的夸大反应的独特特征，并涉及IL-17信号的参与。大剂量全身胆骨化醇可能是局部化疗严重反应的有效治疗方法。我们的研究结果对胆骨化醇作为抗炎症干预过度免疫反应的发展具有广泛的意义。clinicaltrials.gov (NCT02968446)。美国国立卫生研究院和国家关节炎、肌肉骨骼和皮肤疾病研究所（NIAMS；资助U01AR064144、U01AR071168、P30 AR075049、U54 AR079795和P30 AR039750 (CWRU)）。
Adverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D3 on an experimentally induced chemical rash. Skin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks. Cholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement. High-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses. clinicaltrials.gov (NCT02968446). NIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
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发表时间：
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期刊：
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DOI：
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期刊：
The Journal of investigative dermatology
影响因子：
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10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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通讯作者：
Malaguarnera, L.